RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency

Liver Transplantation Clinical Trial

Official title:

A 6-month, Multicenter, Randomized, Open-label Study of Safety and Efficacy of Everolimus-based Regimen Versus Calcineurin Inhibitor (CNI)-Based Regimen in Maintenance Liver Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00267189
• Other study ID #: CRAD001H2401
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2005
• Last updated: April 11, 2011
• Start date: November 2005
• Est. completion date: November 2007

Study information

• Verified date: April 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the effect of everolimus initiation together with reduction or discontinuation of calcineurin inhibitor (CNI) on renal function in maintenance liver transplant recipients with CNI-related renal impairment, while maintaining efficacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria

• Male or female 18 - 70 years old

• Patient who has undergone a primary liver transplantation 12 to 60 months ago from a cadaveric or a living donor

• Patient with a calculated GFR = 60 and = 20mL/min

• Patient receiving tacrolimus with C0-h level = 3 and = 8 ng/mL or Neoral® with C0-h level = 50 and = 150 ng/mL or with C2-h level = 250 ng/mL and = 650 ng/mL with or without any of the following (MPA or AZA or steroids)

• Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 6 months

• Patient in whom an allograft biopsy will not be contraindicated

• Female capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study

Exclusion criteria

• Recipient of multiple solid organ transplants

• Patient on dialysis

• Patient with an identifiable cause of renal dysfunction other than CNI toxicity

• Patient with proteinuria = 1.0 g/24h

• Patient with any acute rejection within 6 months prior to randomization

• Patient with platelet count of = 50,000/mm³ or white blood cell count of = 2,000/mm³ or hemoglobin value = 8 g/dL

• Undergone a liver transplantation for a hepatocellular carcinoma with sign of recurrence;

• Severe graft dysfunction;

• HCV positive patient who needs an active anti-viral treatment

• HIV positive patient

• Patient who is breast feeding

• Patient with a current severe systemic infection

• Patient who has received an unlicensed drug or therapy within one month prior to study entry

• Presence of any hypersensitivity to drugs similar to everolimus (e.g. macrolides)

• Use of any other immunosuppressive drugs than tacrolimus/cyclosporine microemulsion, steroids, azathioprine and mycophenolic acid

Additional protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• Everolimus
1.5 mg bid adjusted in order to achieve a trough level between 3 and 8 ng/mL while in combination with CNI and between 6 and 12 ng/mL after CNI discontinuation
• Calcineurin inhibitors (CNI)

• Mycophenolate acid (MPA)/ Azathioprine (AZA)

• Steroids

Locations

Country	Name	City	State
Germany	Novartis Investigational Site	Germany
Switzerland	Novartis Investigative Site	Basel

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (1)

De Simone P, Metselaar HJ, Fischer L, Dumortier J, Boudjema K, Hardwigsen J, Rostaing L, De Carlis L, Saliba F, Nevens F. Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: a prospective, randomized, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl)	The primary variable was renal function assessed by calculated creatinine clearance using the Cockcroft-Gault formula, and was assessed at all visits.; CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female.	From baseline to 6 months	No
Secondary	Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)	The composite efficacy failure endpoint encompasses at least one of: biopsy proven acute rejection, graft loss, or death for the patient. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy. Acute rejection episodes were recorded as Liver Allograft Rejection. The allograft was presumed to be lost if a patient had a liver retransplant or died.	6 months	No
Secondary	Number of Patients With Discontinuation of Study Medication		6 months	Yes